Exploring the prevalence and risk factors of MASLD in patients with newly diagnosed diabetes mellitus: a comprehensive investigation

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) represents a growing concern in the context of metabolic disorders, particularly among individuals diagnosed with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of MASLD among newly diagnosed T2DM patients and identify the risk factors for MASLD in this population. Methods: This prospective study included 128 patients with newly diagnosed T2DM between January 2022 and June 2023. Demographic, clinical, anthropometric (BMI, waist circumference), and laboratory data (glucose, HbA1c, lipid profile, ALT, AST, creatinine, platelet count) were collected. MASLD was diagnosed based on ultrasonographic evidence of hepatic steatosis with at least one cardiometabolic risk factor after excluding other causes. Linear regression models were used to determine independent predictors. Results: MASLD was detected in 80.4% of patients. Compared with the MASLD (−) group, the MASLD (+) group had significantly higher ALT (47.1 ± 23 U/L vs. 24.9 ± 8 U/L, p < 0.001) and non-HDL cholesterol (189 ± 57 mg/dL vs. 167 ± 28 mg/dL, p = 0.047). Spearman correlation showed positive associations of MASLD severity with waist circumference, LDL cholesterol, and platelet count. ALT and BMI were independently associated with MASLD in linear regression analysis. Conclusions: This study underscores the significant prevalence of MASLD in newly diagnosed T2DM patients, emphasizing the relevance of early detection in addressing this common comorbidity in the diabetic population

Wearable-derived autonomic metrics for predicting metabolic and hepatic risk: insights from AI-READI

This study examined whether wearable-derived autonomic function metrics (WOMAFs) could help predict risk for Type 2 Diabetes and liver fibrosis due to MASLD. While WOMAFs alone had limited predictive value, combining them with clinical measures modestly improved risk stratification using data from the AI-READI dataset

Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction‐Associated Steatotic Liver Disease

ABSTRACTBackgroundMetabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.MethodsWe studied the serum of 87 biopsy‐confirmed MASLD patients and 20 age‐ and sex‐matched control (CTRL) subjects. We first employed an untargeted LC‐MS/MS peptidomics approach (9 CTRL, 32 MASLD) to identify key hits differentially modulated, and subsequently validated the most relevant findings through targeted peptidomics in an enlarged study population (87 MASLD and 20 CTRL).ResultsUntargeted serum peptidomics identified several oxidised apolipoprotein peptide fragments, including ApoE and ApoC‐III, significantly upregulated in MASLD compared to CTRL. Specifically focusing on the oxidative status of intact ApoC‐III, studied through its major glycoforms (ApoC‐III0, ApoC‐IIIi and ApoC‐IIIii), we observed a marked reduction in non‐oxidised forms of these circulating peptides alongside substantially increased levels of their oxidised proteoforms in MASLD versus controls (but not within the disease stages). Oxidised ApoE and ApoC‐III peptide fragments were also significantly correlated with obesity, insulin resistance, dyslipidaemia and transaminases, suggesting a potential link between circulating apolipoprotein oxidation and systemic/hepatic metabolic dysfunction.ConclusionOur data reveals a previously unreported oxidised apolipoprotein profile associated with MASLD. The functional and clinical implications of these findings warrant further mechanistic investigation.</jats:sec

Hepatic fatty acid and glucose handling in metabolic disease: potential impact on cardiovascular disease risk

The prevalence of metabolic diseases, including type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing. Although invariably associated with obesity, the importance of fat deposition in non-adipose tissue organs has yet to be fully explored. Pathological ectopic fat deposition within the liver (known as (MASLD)) has been suggested to underlie the development of T2DM and is now emerging as an independent risk factor for cardiovascular disease (CVD). The process of hepatic de novo lipogenesis (DNL), that is the synthesis of fatty acids from non-lipid precursors (e.g. glucose), has received much attention as it sits at the intersect of hepatic glucose and fatty acid handling. An upregulation of the DNL pathway has been suggested to be central in the development of metabolic diseases (including MASLD, insulin resistance, and T2DM). Here we review the evidence to determine if hepatic DNL may play a role in the development of MASLD and T2DM and therefore underlie an increased risk of CVD

Impact of PNPLA3 I148M on Clinical Outcomes in Patients With MASLD

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a heterogenous clinical and histopathological entity, where multiple metabolic co-factors are intertwined with high interindividual variability. The impact and severity of each factor (including obesity and type 2 diabetes) define a systemic dysmetabolism that can lead to either advanced liver disease and its complication (including hepatocellular carcinoma and clinical events related to portal hypertension) or extrahepatic events: incident cardiovascular disease, chronic kidney disease and extrahepatic cancers. The balance between environmental factors and genetic susceptibility has unique implications in MASLD: the intermittent injury of metabolic co-factors, their fluctuation over time and their specific management, are counterbalanced by the presence of gene variants that can significantly impact the disease at multiple levels. The I148M variant in the PNPLA3 gene is the most investigated genetic susceptibility that induces a more severe steatohepatitis, enhanced fibrogenesis and can shape the incidence of long-term clinical events regardless of, or worsened by, other metabolic risk factors. Methods and results: In this review, we will summarise the updated evidence on the natural history of MASLD accounting for classical metabolic risk factors, the role of PNPLA3 in clinical sub-phenotyping (e.g., 'lean MASLD'), impact on disease severity and fibrosis progression, as well as its role for prognostication, alone or in combination with non-invasive tools into polygenic risk scores

Global burden of metabolic diseases, 1990-2021

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex.METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI).RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]).CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.</p